This invention relates to an improved process for conversion of a hydroxy derivative to the corresponding fluoro compound. More particularly, this invention relates to a process for converting substituted hydroxy-oxazoline compounds to the corresponding substituted fluoro derivatives. The latter compounds are useful intermediates in the preparation of D-(threo)-1-aryl-2-acylamido-3-fluoro-1-propanol compounds which are antibacterial agents.
U.S. Pat. No. 4,235,892 discloses D-(threo)-1-aryl-2-acylamido-3-fluoro-1-propanol compounds which are known in the art as broad spectrum antibacterial agents useful in the treatment of gram positive, gram negative and rickettsial infections. A preferred compound disclosed in the noted patent is D(-)-threo-1-(4-methylsulfonyl phenyl)-2-dichloroacetamido-3-fluoro-1-propanol, also known as florfenicol.
U.S. Pat. No. 4,311,857 discloses methods of preparing D-(threo)-1-aryl-2-acylamido-3-fluoro-1-propanols by reacting D-(threo)-1-aryl-2-N-protectedamino-1, 3-propanediol with dialkylaminosulfur trifluoride followed by removal of the N-protecting group and then reacting the resulting D-(threo)-1-aryl-2-amino-3-fluoro-1-propanol with a lower alkanoic acid derivative.
European Patent Application 130,633 discloses oxazoline and oxazolidinone compounds useful as intermediates in preparing 1-aryl-2-amino-3-fluoro-1-propanol compounds. This patent application discloses that the primary hydroxy group of the appropriately substituted oxazoline and oxazolidinone derivatives can be replaced by fluorine utilizing various fluorinating agents; such as phosphorous fluorides, hydrofluoric acid and 2-chloro-1,1,2-trifluorotriethylamine also referred to as the Yarovenko reagent. When the latter reagent is employed as the fluorinating agent, the reaction is carried out under anhydrous conditions and in homogeneous phase, preferably in actonitrile at the boiling point temperature. The fluoro oxazoline derivative which results from the known process is then converted by a series of steps, all of which are known in the art, to the desired D-(threo)-1-aryl-2-amino-3-fluoro-1-propanol compounds.
We have now found that fluoro-substituted oxazoline compounds can be prepared in unexpectedly higher yields from hydroxy oxazoline compounds by reacting the latter compounds with .alpha.,.alpha.-difluoroalkylamine fluorinating reagents under pressure rather than by carrying out the reaction in a solvent or diluent at reflux.